RT Journal Article
SR Electronic
T1 The expanding role of fish models in understanding non-alcoholic fatty liver disease
JF Disease Models & Mechanisms
JO Dis Models Mech
FD The Company of Biologists Limited
SP 905
OP 914
DO 10.1242/dmm.011981
VO 6
IS 4
A1 Asaoka, Yoichi
A1 Terai, Shuji
A1 Sakaida, Isao
A1 Nishina, Hiroshi
YR 2013
UL http://dmm.biologists.org/content/6/4/905.abstract
AB Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC). NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio) and medaka (Oryzias latipes). Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH) pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.